Rpd3-dependent boundary formation at telomeres by removal of Sir2 substrate

Ehrentraut, Stefan; Weber, Jan; Dybowski, J. Nikolaj; Hoffmann, Daniel; Ehrenhofer‐Murray, Ann E.

doi:10.1073/pnas.0909169107

Cited by 53 publications

(72 citation statements)

References 40 publications

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“…A second possibility is that Sir2 within silent chromatin acts far beyond the nucleosomes to which it is bound, thereby creating zones of potential Sir3 binding sites. A final possibility is that additional deacetylases, such as Rpd3, participate in creating transition zones (Ehrentraut et al 2010).…”

Section: Barriers and Antisilencingmentioning

confidence: 99%

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

2016

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Transcriptional silencing in Saccharomyces cerevisiae occurs at several genomic sites including the silent mating-type loci, telomeres, and the ribosomal DNA (rDNA) tandem array. Epigenetic silencing at each of these domains is characterized by the absence of nearly all histone modifications, including most prominently the lack of histone H4 lysine 16 acetylation. In all cases, silencing requires Sir2, a highly-conserved NAD + -dependent histone deacetylase. At locations other than the rDNA, silencing also requires additional Sir proteins, Sir1, Sir3, and Sir4 that together form a repressive heterochromatin-like structure termed silent chromatin. The mechanisms of silent chromatin establishment, maintenance, and inheritance have been investigated extensively over the last 25 years, and these studies have revealed numerous paradigms for transcriptional repression, chromatin organization, and epigenetic gene regulation. Studies of Sir2-dependent silencing at the rDNA have also contributed to understanding the mechanisms for maintaining the stability of repetitive DNA and regulating replicative cell aging. The goal of this comprehensive review is to distill a wide array of biochemical, molecular genetic, cell biological, and genomics studies down to the "nuts and bolts" of silent chromatin and the processes that yield transcriptional silencing.

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Section: Barriers and Antisilencingmentioning

confidence: 99%

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

2016

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“…We also observed regions of H4K16 hypoacetylation without detectable Sir2 association, which presumably reflected the action of a different histone deacetylase such as Rpd3 or Hst1. Both have been shown to associate with subtelomeric chromatin (Kurdistani et al 2002;Ehrentraut et al 2010;Li et al 2013). Alternatively, the hyopacetylation of H4K16 in these regions could be due to transient Sir2 association not captured by ChIP-Seq.…”

Section: Catalytic Activity Of Sir2 At Telomeresmentioning

confidence: 99%

The Chromatin and Transcriptional Landscape of NativeSaccharomyces cerevisiaeTelomeres and Subtelomeric Domains

2015

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Saccharomyces cerevisiae telomeres have been a paradigm for studying telomere position effects on gene expression. Telomere position effect was first described in yeast by its effect on the expression of reporter genes inserted adjacent to truncated telomeres. The reporter genes showed variable silencing that depended on the Sir2/3/4 complex. Later studies examining subtelomeric reporter genes inserted at natural telomeres hinted that telomere position effects were less pervasive than previously thought. Additionally, more recent data using the sensitive technology of chromatin immunoprecipitation and massively parallel sequencing (ChIP-Seq) revealed a discrete and noncontinuous pattern of coenrichment for all three Sir proteins at a few telomeres, calling the generality of these conclusions into question. Here we combined the ChIP-Seq of the Sir proteins with RNA sequencing (RNA-Seq) of messenger RNAs (mRNAs) in wild-type and in SIR2, SIR3, and SIR4 deletion mutants to characterize the chromatin and transcriptional landscape of all native S. cerevisiae telomeres at the highest achievable resolution. Most S. cerevisiae chromosomes had subtelomeric genes that were expressed, with only 6% of subtelomeric genes silenced in a SIR-dependent manner. In addition, we uncovered 29 genes with previously unknown cell-type-specific patterns of expression. These detailed data provided a comprehensive assessment of the chromatin and transcriptional landscape of the subtelomeric domains of a eukaryotic genome.KEYWORDS Sir complex; telomeres; ChIP-Seq; RNA-Seq; mating-type regulation T ELOMERES are specialized structures at the ends of eukaryotic chromosomes that are critical for various biological functions. Telomeres bypass the problem of replicating the ends of linear DNA, protect chromosome ends from exonucleases and nonhomologous end joining, prevent the linear DNA ends from activating a DNA-damage checkpoint, and exhibit suppressed recombination [reviewed in Wellinger and Zakian (2012)]. In Saccharomyces cerevisiae, telomeres are composed of three sequence features: telomeric repeats, which consist of 300 6 75 bp of (TG 1-3 ) n repeated units produced by telomerase; X elements; and Y9 elements, which contain an ORF for a putative helicase gene. The X elements are subdivided into a core X [consisting of an autonomously replicating sequence (ARS) consensus sequence and an Abf1-binding site] and subtelomeric repeats that have variable numbers of repeated units containing a binding site for Tbf1 (Louis 1995). All telomeres contain telomeric repeats plus an X element, and about half of S. cerevisiae's 32 telomeres also contain a Y9 element (X-Y9 telomeres). X-only telomeres contain an X element but not a Y9 element. Unlike the Y9 elements, the telomeric repeats and X elements are bound by proteins that are critical for maintenance of telomeres. Rap1 binds the TG 1-3 telomeric repeats and recruits the Sir2/3/4 protein complex, the trio of heterochromatin structural proteins critical for repression of the silent mating ...

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“…RPD3, SIN3, UME1, SPA30 and PHO23) of the Rpd3 complex, mutation of DEP1 displays a thermosensitive growth phenotype (Ruiz-Roig et al, 2010). The Rad3 complex is known to be involved not only in cell adaptation during the heat stress response but also in regulating heterochromatic boundary that restricts the spread of gene silencing (Ehrentraut et al, 2010;Zhou et al, 2009). In fact, deletion of DEP1 reduces the transcription of subtelomeric genes.…”

Section: Discussionmentioning

confidence: 99%

Sphingolipids regulate telomere clustering by affecting transcriptional levels of genes involved in telomere homeostasis

Ikeda

Muneoka

Murakami

et al. 2015

Journal of Cell Science

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In eukaryotic organisms, including mammals, nematodes and yeasts, the ends of chromosomes, telomeres are clustered at the nuclear periphery. Telomere clustering is assumed to be functionally important because proper organization of chromosomes is necessary for proper genome function and stability. However, the mechanisms and physiological roles of telomere clustering remain poorly understood. In this study, we demonstrate a role for sphingolipids in telomere clustering in the budding yeast Saccharomyces cerevisiae. Because abnormal sphingolipid metabolism causes downregulation of expression levels of genes involved in telomere organization, sphingolipids appear to control telomere clustering at the transcriptional level. In addition, the data presented here provide evidence that telomere clustering is required to protect chromosome ends from DNA-damage checkpoint signaling. As sphingolipids are found in all eukaryotes, we speculate that sphingolipid-based regulation of telomere clustering and the protective role of telomere clusters in maintaining genome stability might be conserved in eukaryotes.

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Rpd3-dependent boundary formation at telomeres by removal of Sir2 substrate

Cited by 53 publications

References 40 publications

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

The Chromatin and Transcriptional Landscape of NativeSaccharomyces cerevisiaeTelomeres and Subtelomeric Domains

Sphingolipids regulate telomere clustering by affecting transcriptional levels of genes involved in telomere homeostasis

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